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Fentanyl Does Not Alter the "Sleep" Plasma Concentration of Thiopental

Departments of Anesthesia, Saint George's Hospital, London, England, and Duke University Medical Center, Durham, North Carolina

Abstract

Thiopental and fentanyl are commonly combined for induction of anesthesia. The effect of an analgesic concentration of fentanyl on the plasma concentration of thiopental to induce sleep was studied in 46 unpremedicated patients. As a measure of drug effect, sleep (the lack of response to open eyes to a verbal command) was used. Forty-six patients were randomized to receive thiopental infused to one of several predetermined plasma concentrations. Twenty-two of these patients also received a fentanyl infusion to a desired analgesic concentration of 1 ng/mL. Thiopental and fentanyl were infused by means of a pharmacokinetic model-driven infusion device (computer-assisted continuous infusion, CACI). Venous blood samples were taken from the contralateral antecubital fossa at 5 and 10 min after the start of the infusion. At 10 min, the patients' names were firmly spoken, and they were instructed to open their eyes. If they did not respond to this command, they were considered to be asleep. Only patients in whom the 5– and 10-min measured plasma concentrations of thiopental and fentanyl, respectively, were within ±30% of each other were used for the determination of the Cp50(asleep), the plasma concentration at which 50% of the patients were asleep. The Cp50(asleep) with and without fentanyl was calculated by logistic regression. The Cp50(asleep) for patients in whom concentrations were maintained within ±30% for thiopental alone (n = 17) was 7.32 µg/mL (95% confidence interval, 5.53–10.95); for thiopental in the presence of fentanyl (n = 18 with a measured fentanyl concentration of 1.27 ± 0.5 ng/mL), this was 7.22 µg/mL (95% confidence interval, 4.83–10.15). There was no interaction between fentanyl (up to a concentration of 2.1 ng/mL) and the Cp50(asleep) for thiopental. We conclude that fentanyl, at an analgesic concentration, has no effect on the hypnotic concentration of thiopental.

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